The ultimate goal of this research is to characterize the forces directing RNA folding, and to use this knowledge to reliably predict structures of RNA molecules from their sequences. Since most diseases are mediated through RNA, and some viruses, including AIDS, are RNA, the results can lead to rational design of drugs. The results should also further the interpretation of sequences determined by the Human Genome Project. The foundation for structure prediction will be provided by studies of the thermodynamic and structural properties of oligonucleotides. Our understanding of the principles governing RNA folding will be tested by comparing predicted and known secondary structures, and by studies of the folding mechanism of the self splicing intervening sequence from the ribosomal RNA precursor in Tetrahymena thermophila.